BP1, a homeoprotein, is significantly expressed in prostate adenocarcinoma and is concordant with prostatic intraepithelial neoplasia.
BP1 is a member of the homeobox gene superfamily of transcription factors that are essential for early development. Significant mRNA expression and immunohistochemical reactivity of BP1 is present in a majority of breast cancers and in all cases of inflammatory breast cancer. This study attempts to determine whether BP1 expression is detectable in prostate cancer, another hormone dependent solid tumor, and whether this expression correlates with histopathologic and prognostic factors. Paraffin sections from radical prostatectomy cancer specimens and from tissue microarray sections of prostate cancer, obtained from the Prostate Cancer Tissue Registry (NIH), were assayed for BP1 immunoreactivity. Immunoreactivity scoring by two independent pathologists, using a three-tiered system (0, 1+, 2+), was recorded and correlated with Gleason scoring and prostatic specific antigen (PSA) biochemical recurrence. Ki-67 (MIB-1) immunoreactivity was performed to assess proliferation. Kappa and Cochran-Mantel-Haenszel statistical analyses were used to assess interobserver agreement and pathobiologic correlations. Significant BP1 immunoreactivity (2+) was identified in approximately 70% of prostatic adenocarcinomas, whether the analysis was performed on tissue sections (50 cases) or tissue microarray platforms (123 cases). BP1 immunoreactivity was seen in <5% of normal acinar cells. The agreement between two separate observers was very good, with kappa-statistics >0.7. In tissue sections, 12 cases with paired carcinoma and prostatic intraepithelial neoplasia (PIN) showed concordance with strong immunoreactivity. Gleason scores or prostatic specific antigen (PSA) biochemical recurrences were not correlated with strong BP1 immunoreactivity. Tumor proliferation, assayed with Ki-67 (MIB-1) immunoreactivity, was higher in cancer cells that were BP1 immunoreactive, relative to those that were BP1 non-reactive. These findings suggest that BP1 is an important upstream factor in the carcinogenic pathway of prostate cancer and that the expression of BP1 may reflect or directly contribute to tumor progression and/or invasion.
Schwartz
Arnold M
AM
Department of Pathology, The George Washington University Medical Center, Washington DC 20037, USA. aschwartz@mfa.gwu.edu
Man
Yan-Gao
YG
Rezaei
M Katayoon
MK
Simmens
Samuel J
SJ
Berg
Patricia E
PE
D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D018398:Homeodomain Proteins / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood; D019048:Prostatic Intraepithelial Neoplasia / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; C105304:DLX4 protein, human; D018398:Homeodomain Proteins; D014157:Transcription Factors; D017430:Prostate-Specific Antigen